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tRNA homeostasis and gene regulation

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Another function for tRNA?

Recent discoveries relate changes in transfer RNA (tRNA) abundance to apoptosis and gene misregulation in tumourigenic cells. A European study investigated the processes affecting tRNA abundance under stress.

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tRNA is a necessary component of protein synthesis. It transfers an amino acid to a growing polypeptide chain during translation. Recent reports show that the abundance of the total tRNA pool can vary during the cell cycle. Demonstrating that the tRNA pool in the cell is adaptable will add a new regulatory level with important implications for cell biology. The EU-funded TRNA DYNAMICS (tRNA homeostasis and gene regulation) project studied tRNA abundance in yeast as a model organism. The project quantitatively studied tRNA homeostasis, which was altered under diverse stress conditions. The project investigated whether transcription, nucleo-cytoplasmic transport and degradation varied for individual tRNAs coding for different amino acids. The effects of altered tRNA dynamics on protein abundance and cell fitness were assessed under different cellular conditions. Results showed that individual tRNAs changed under stress conditions in yeast in a time-dependent manner. During stress, the changes were mostly related to tRNA degradation. A stress-related ribonuclease was identified as a key player in the specific regulation of tRNAs. Scientists also found that tRNA abundance was affected by tRNA shuttling between nucleus and cytoplasm. The active shuttling occurred during stress and was dependent on the stress condition. The changes in tRNA abundance impacted protein synthesis and thus can be considered a new regulatory layer in the cell. TRNA DYNAMICS results support the concept that tRNA abundance is tightly controlled in the cell and regulates protein synthesis in the ribosome. Better understanding of tRNA availability regulation and its connection to cell survival could potentially empower the design of new molecular therapies for cancer.

Keywords

Transfer RNA, apoptosis, tRNA abundance, cell cycle, homeostasis, gene regulation

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